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• 产品描述： Afatinib (BIBW 2992) dimaleate is an orally active, potent and irreversible dual specificity inhibitor of ErbB family (EGFR and HER2), with IC50 values of 0.5 nM, 0.4 nM, 10 nM and 14 nM for EGFRwt, EGFRL858R, EGFRL858R/T790M and HER2, respectively. Afatinib dimaleate can be used for the research of esophageal squamous cell carcinoma (ESCC), non-small cell lung cancer (NSCLC) and gastric cancer

• 靶点： EGFR:0.5 nM (IC50);HER2:14 nM (IC50);EGFRL858R:0.4 nM (IC50);EGFRL858R/T790M;10 nM (IC50)

• 体外研究： Afatinib dimaleate (100 nM) sufficiently prevents heregulin-stimulated HER3 phosphorylation. Afatinib dimaleate (0-10000 nM) effectively inhibits anchorage-independent proliferation of NIH-3T3 cells ectopically expressing EGFR mutants, and inhibits cell proliferation of H1666, H3255, and NCI 1975 cells. Afatinib dimaleate (48-72 h)shows growth inhibition in HKESC-1, HKESC-2, SLMT-1 and EC-1 cells. Afatinib dimaleate (0-1 μM, 24-48 h) inhibits AKT and MAPK pathways, and inhibits EGFR and AKT phosphorylation in ESCC cell lines. Afatinib dimaleate (0-1 μM, 16-48 h) induces G0/G1 cell cycle arrest in HKESC-2 and EC-1. Afatinib dimaleate (0-1 μM, 24-48 h) effectively induces apoptotic cell death in HKESC-2 and EC-1. Cell Proliferation Assay Cell Line: NIH-3T3 cells, H1666, H3255, and NCI 1975 cells Concentration: 0, 1, 10, 100, 1000, 10000 nM Incubation Time: Result: Effectively inhibited anchorage-independent proliferation of NIH-3T3 cells ectopically expressing EGFR mutants. Showed inhibition of anchorage independent cell proliferation of various lung cancer cell lines (H1666, H3255, and NCI 1975 cells), with IC50 values of 60 nM, 0.7 nM and 99 nM, respectively. Cell Viability Assay Cell Line: HKESC-1, HKESC-2, SLMT-1 and EC-1 cell lines Concentration: Incubation Time: 48 and 72 hours Result: Observed over 95% of growth inhibition. The respective IC50 concentrations at 48 hours (HKESC-1=0.078 μM, HKESC-2=0.115 μM, KYSE510=3.182 μM, SLMT-1=4.625 μM and EC-1=1.489 μM) and 72 hours (HKESC

• 体内研究： Afatinib dimaleate (0-20 mg/kg, Orally, daily for 25 days) shows dramatic tumor regression and downregulation of EGFR, HER2, HER3 and AKT phosphorylation. Afatinib dimaleate (15 mg/kg, Orally, in a schedule of 5 days on plus 2 days off, for two weeks) strongly inhibits the growth of HKESC-2 tumor. Animal Model: Athymic NMRI-nu/nu female mice (21–31 g, five to six-week-old, transgenic murine lung cancer model and xenograft models) Dosage: 15 mg/kg, 20 mg/kg Administration: Orally, daily for 25 days Result: Resulted in dramatic tumor regression with a cumulative treated/control tumor volume ratio (T/C ratio) of 2% in a standard xenograft model of the epidermoid carcinoma cell line A431, and downregulation of EGFR and AKT phosphorylation. Induced regression of large tumors in this HER2-driven model, effectively controlled xenograft tumor formation by the NCIH1975 cell line, expressing EGFR L858R/T790M, with a T/C value of 12% for doses of 20 mg/kg. Induced more than 50% percent tumor reduction after a 4-week treatment period. Downregulated EGFR, HER2 and HER3 phosphorylation. Animal Model: Six weeks old female athymic nude mice (nu/nu) (16-20 g) Dosage: 15 mg/kg Administration: Oral gavage in a schedule of 5 days on plus 2 days off, for two weeks Result: Strongly inhibited the growth of HKESC-2 tumor. Average tumor sizes of vehicle and treatment at end point are 348 ± 24 mm3 and 108 ± 36 mm3 respectively.

• 参考文献：
  1. Li D, et al. BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models. Oncogene. 2008 Aug 7;27(34):4702-11. 2. Wong CH, et al. Preclinical evaluation of afatinib (BIBW2992) in esophageal squamous cell carcinoma (ESCC). Am J Cancer Res. 2015 Nov 15;5(12):3588-99 3. Wang XK, et al. Afatinib circumvents multidrug resistance via dually inhibiting ATP binding cassette subfamily G member 2 in vitro and in vivo. Oncotarget. 2014 Dec 15;5(23):11971-85. 4. Yoshioka T, et al. Antitumor activity of pan-HER inhibitors in HER2-positive gastric cancer. Cancer Sci. 2018 Apr;109(4):1166-1176.

• 溶解性： Soluble  in  DMSO、H2O

• 保存条件： -20℃

• 配置溶液浓度参考：
  

  	1mg	5mg	10mg
  1 mM	1.393 ml	6.963 ml	13.926 ml
  5 mM	0.279 ml	1.393 ml	2.785 ml
  10 mM	0.139 ml	0.696 ml	1.393 ml
  50 mM	0.028 ml	0.139 ml	0.279 ml

• 注意：部分产品我司仅能提供部分信息，我司不保证所提供信息的权威性，仅供客户参考交流研究之用。

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本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系，公式为：

质量 (mg) = 浓度 (mM) x 体积 (mL) x 分子量 (g/mol)

• pg ng μg mg g kg =
  fM pM nM μM mM M *
  nL μL mL L *